Phosphoinositide 3-kinases (PI3Ks) are signaling molecules involved in numerous cellular functions such as cell cycle, cell motility and apoptosis. PI3Ks are protein and lipid kinases that produce second messenger molecules activating several target proteins including small GTPases like Ras, Rho, Rac and Cdc42 and serine/threonine kinases like PDK1 and Akt/PKB. This latter kinase phosphorylates and inhibits two important players in the apoptotic machinery, BAD and Caspase-9. Furthermore, PKB modulates the activity of GSK3, mTOR, p70S6K and FOX transcription factors, eventually controlling cell proliferation. Accordingly to this view, PI3Ks are known to act as oncogenes by amplification or mutation (Cully et al., 2006; Vivanco and Sawyers, 2002). Moreover, PTEN, the enzyme which de-phosphorylates phosphoinositides at the D-3 hydroxy position of the inositol ring, functions as a potent anti-oncogene. Altogether these observations strongly indicate that metabolism of PtdIns 3-phosphates is directly involved in the oncogenic process and that PI3Ks might be key regulators of the transformed phenotype.
PI3Ks are divided in three classes and class I comprises four different PI3Ks named α, β, γ and δ. Class IA PI3Ks are mainly activated by tyrosine kinase receptors and are heterodimers composed of a p110 catalytic subunit and a p85 regulatory subunit. PI3Kβ (p110β) is a class IA member that is ubiquitously expressed and possesses the unique feature of being activated not only by tyrosine kinase receptors, but also by G protein-coupled receptors (Vanhaesebroeck et al., 2001). Presently, little is known about the specific in vivo function of the PI3Kβ isoform.